The overall goal of this project is to use autoimmune thyroid disease as a model for determining the underlying pathologic mechanisms in human autoimmune disease. The project has four specific aims that examine cellular aspects of the autoimmune response to thyroid antigens. The first specific aim seeks to determine the antigen specificity and T cell receptor (TCR) structure of intrathyroidal human T cells. Specific Aim II focuses on the cloning and characterization of TSH receptor specific human T cells. The investigators plan on using a unique system where they transfect EB virus transformed B cells from the patient with the cDNA for the TSH receptor and use these B cells as antigen presenting cells to evolve T cell clones. Specific Aim III involves an evaluation of the induction of the anergy in T cells responding to thyroid antigens, examining both T cell lines evolved from intrathyroidal tissue and T cell clones produced in Specific Aim II. If resistance to the induction of anergy is seen in these T cells, then the mechanism of this resistance will be evaluated. Finally, Specific Aim IV seeks to identify peptide analogues of TSH receptor amino acid sequences that can be used to inhibit T cell responsiveness to the receptor.